The overall objectives of this proposal are to determine the epidemiology and best prevention regimens for cytomegalovirus (CMV) infection for pediatric lung transplant recipients. In pediatric lung transplantation, CMV infection occurs in 23% of recipients and was associated with a four-fold increase in death or retransplantation in a single-center study. The optimal methods for prevention of CMV infection are uncertain. Further, the specific side effect profile of CMV prevention regimens has not been documented in this population. The data gained in pursuit of these studies will provide background information for the development of prospective clinical trials to answer the questions of how to best prevent infection related morbidity and mortality in pediatric lung transplant recipients. The following aims will be accomplished (1) extension of the single-center pilot trial initiated by the applicant to evaluate the feasibility, toxicity and short-term efficacy of prolonged intravenous ganciclovir; (2) assessment of valganciclovir (VGCV) side effects in adult lung transplant recipients; and (3) a multi-center study with subjects from at least 11 clinical sites. The pilot study aims to determine the feasibility, safety and short-term efficacy of prolonging ganciclovir prophylaxis from 6 weeks to 12 weeks in pediatric lung transplant recipients. The adult pilot study aims to assess the side effect profile of oral VGCV in adult lung transplant recipients. The multi-center study aims to evaluate the impact of CMV infection on death/retransplantation and other transplant-related morbidity in the first year after transplantation as well as to evaluate the impact of CMV hyperimmune globulin (CMVIG) on the rate of CMV infection. While accomplishing these aims, the applicant will have the opportunity to complete a structured 5-year career development program to develop into an independent clinical investigator. The objectives of the career development plan include, 1) advanced training in research methods, epidemiology, biostatistics, virology and immunology, 2) use of patient-oriented research approach to confirm the impact of a modifiable infection in pediatric lung transplant recipients in the first year after pediatric lung transplantation and to determine the impact of various preventative regimens for CMV during the first year after pediatric lung transplantation, 3) using the results of the patient-oriented research to develop prospective intervention trials to decrease the morbidity and mortality associated with CMV in pediatric lung transplant recipients, and 4) development into a physician scientist in Pediatric Infectious Diseases performing independent patient-oriented research in a major academic center. Specific studies in pediatric lung transplant recipients evaluating the feasibility of prolonged prevention regimens, the impact of CMV infection and role of various prevention regimens are needed to reduce morbidity and mortality after pediatric lung transplantation. Estimating the side effects of VGCV in adult lung recipients will expedite the transition to oral agents in children. After completion, the applicant will have sufficient preliminary data to propose a multi-center prevention trial for CMV infection in pediatric lung transplant recipients.